Role of heparan sulfate in initiation and propagation of islet amyloid polypeptide aggregation
Kailash Singh
Islet amyloid poly peptide (IAPP) is a β-cell hormone produced and secreted together with insulin in response to glucose. Under normal condition, IAPP participates in the regulation of blood glucose homeostasis, but under certain circumstances such as type 2 diabetes IAPP can misfold and form cell toxic amyloid. Not much is known about why amyloid forms, but I have with the described work studied if proteoglycans has any role in the amyloid initiation process. To do this, I have characterized the expression of proteoglycans in β-cell, and identified heparan sulfate as the main carbohydrate chain on β-cell and islet of Langerhans.
After culturing β-cells at different glucose concentrations I could show an alteration of heparan sulfate chain lengths. An in vivo study was performed where the effect of short heparan sulfate related fragments on IAPP amyloidogenesis in transplanted islets was investigated. So far our findings support further analysis of heparan sulfate role in IAPP amyloid formation.
Kailash Singh
Degree Project in Biology (Immunology), Master of Science (2 years), 2011 Examensarbete i biologi 45 hp till masterexamen , 2011
Department of Medical Cell Biology, Uppsala University Supervisor: Professor Gunilla T. Westermark